Asthma, COPD and Respiratory Infections Flashcards

Question

What pathology may alter the transmural pressure gradient and how?

Answer 1

Pneumothorax (air in pleural space) ≈ Spontaneous or Traumatic pneumothorax ≈ intrapleural pressure increases = lung = reduce transmural pressure gradient across lung wall ≈ collapsed lung which fails to inflate due to changes in pressure  

Answer 2

Spirometry

Answer 3

* TV = 0.5L * IRV = 3L * IC (TV + IRV) = 3.5L * ERV = 1L * RV = 1.2L * FRC (ERV + RV) = 2.2L * VC (IC + ERV) = 4.5L * TLC (IC + FRC) = 5.7L

Answer 4

TLC - (TV+ ERV + RV)

Answer 5

IRV + TV + ERV

Answer 6

TLC - (IRV + TV + ERV) OR FRC - ERV

Answer 7

Restrictive lung disease ≈ reduced inspiration ≈ reduced inspiratory volume ≈ reduced VC + reduced TLC + reduced IRV  

Answer 8

Restrictive Lung Diseases (Sarcoidosis, Asbestosis, Pulmonary fibrosis) • Reduced compliance ≈ reduced inspiration ≈ reduced inspiratory volume ≈ reduced VC + reduced TLC + reduced IRV • FEV/FVC < 0.7

Answer 9

Obstructive Lung Diseases (COPD, asthma, bronchiectasis, bronchitis) • Reduced elasticity ≈ reduced expiration ≈ reduced expiratory volume ≈ increased TLC due to increased RV • FEV/FVC <<< 0.7

Answer 10

Not all inspired air gets to alveoli and partakes in gas exchange thus part remains in conducting airways where no gas exchange occurs ≈ anatomical dead space ≈ airway dead space ≈ 150mL ≈ volume of conducting airways

Answer 11

500mL breathed per tidal volume but only 350mL reaches site of gas exchange

Answer 12

Volume of physiological dead space likely to be higher in subjects with lung disease

Answer 13

Pulmonary Ventilation • Volume of air breathed in and out in 1 minute * PV = TV x RF * 6L/min = 500mL x 12bpm Alveolar Ventilation • Volume of air exchanged between atmosphere and alveoli per minute * AV = (TV-DS) x RF * 4.2L/min = (500-150mL) x 12bpm

Answer 14

Increase pulmonary ventilation

Answer 15

Increase pulmonary ventilation

Answer 16

Increase alveolar ventilation

Answer 17

Alveolar ventilation would decrease

Answer 18

Increasing tidal volume

Answer 19

* Conjunctiva * Respiratory tract: Oral/Sinus/Middle ear/Trachea/Lungs * GI tract: Oesophagus/Stomach/Intestine * Urogenital tract: Kidney/Ureter/Uretus/Bladder/Vagina * Mammary gland

Answer 20

Epithelial layers line organs/surfaces exposed to external world ≈ delicate and protected on external mucosal surfaces (mucous secretions, AMPs and dimeric IgA) + submucosal layer (lamina propria ≈ loose CT)

Answer 21

* Plasma cells secrete dimeric IgA * IgA binds BL surface @ PIgR (polymeric Ig Receptor) * Endocytosis * Transcytosis  apical * Release of IgA at apical epithelial cell

Answer 22

* Innate Lymphoid Cells: Direct response * Mast cells: IgE * Eosinophils: IgE * Macrophages: Phagocytosis and APC * Dendritic cells: APC * T lymphocytes: Memory * Plasma Cells: IgA, IgG, IgM and IgE * Mucosa Associated Lymphoid Tissue (MALT): upregulation  iMALT

Answer 23

1) Airway Surface Liquid • Gel layer • Periciliary fluid layer • Cilia ``` 2) Epithelium • Cuboidal epithelial layers • Goblet cells • Basal cells • Basement membrane ``` ``` 3) Lamina Propria • Smooth muscle • Connective tissue • Blood vessels • Lymph vessels ``` 4) Cartilaginous Layer • Cartilage

Answer 24

* Mucosal Associated Lymphoid Tissue (MALT) = accumulation of lymphoid tissue ordered by lymphoid follicles and germinal centers can be upregulated * Submucosal dendritic cells carry processed antigen to MALT/BALT --> present to Th2 lymphocytes --> IL-4, IL-5, IL-13 --> Eosinophils --> IgA, IgG, IgE --> hypersensitivity

Answer 25

* Bronchial associated lymphoid tissue = BALT * iBALT (inducible) vs cBALT (constitutive) iBALT • Upregulated • Less ordered • Intraepithelial lymphocytes, lymphoid follicle and marginal T cell zone cBALT • Constitutive • Ordered • Regional lymph node with defined areas: Paracortical region (T) and 1º lymphoid follicle (B) and medulla

Answer 26

1) Anatomical Features • Mucosal vs Lymphoid tissues • Discrete compartments of diffuse lymphoid tissue vs organised structures: Peyer’s Patches, Isolated lymphoid follicles and tonsils • Specialised antigen-uptake: M cells --> Peyer’s Patches; IgA via PIgR 2) Effector Mechanisms • T cells • IgA secretion • Microbiota 3) Immunoregulatory Environment • Down-regulation of immune responses • Up-regulation of immune responses • Inhibitory macrophages and tolerance-inducing dendritic cells

Answer 27

Specific soluble antigen binds Naive B cells and travels in circulation to lymph nodes ≈ present processed antigen to T follicular helper cells (CD4+ T helper cells) in MHC Class II molecules ≈ Activated T follicular helper cell recognises specific antigenic peptide with MHC class II ≈ cytokine secretion (IL-4, IL-5, IL-6, IL-9, IL-10, IL-13) ≈ mediate B cell proliferation (of B cell with that BCR) and class switching ≈ plasmablasts form 1º focus ≈ further differentiation proceed to germinal centre ≈ memory cells or antibody-secreting

Answer 28

Asthma is an IgE-mediated lower respiratory allergic reaction ≈ hypersensitivity reaction (Type I)

Answer 29

Stimuli:  - Dander (cat)   - Pollens   - HDM    Route of entry:   - Respiratory tract inhalation ≈ contact with mucosal lining of lower airways    

Answer 30

``` Response:  - Bronchial constriction (C)  - Increased mucus production (M)  - Airway inflammation (I)  - Bronchial hyper-reactivity (H)   Mnemonic: CHIM ```

Answer 31

Reversible airway inflammation with heterogeneous aetiology: allergens (foreign antigens that cause hypersensitivity: plant, fungal, HDM, Der p 1, cat dander, cockroach…)--> activation of submucosal mast cells and basophils of LRT --> degranulation ≈ bronchial constriction + increased mucous secretion --> wheeze, dyspnoea, tightness, cough and variable expiratory airflow limitation

Answer 32

* Allergic * Exercise-induced * Neutrophil predominant

Answer 33

Genetic tendency to produce IgE to common environmental proteins (allergens) to mediate a hypersensitivity reaction, developing classic allergic diseases: atopic dermatitis, allergic rhinitis and asthma

Answer 34

* Dermatitis * Allergic Rhinitis * Allergic Asthma

Answer 35

* Reversible airway inflammation of heterogeneous origin * Sx: Wheeze, SOB, Tightness, Cough * Variable expiratory airflow limitation

Answer 36

Allergens (HDM, dander, cockroaches, pollen, mold) enters respiratory tract --> phagocytosis by dendritic cells --> taken to a naïve T-lymphocyte in the Paracortical area of lymph node --> APC to mediate Th-2 response --> IL-4, IL-5, IL-9, IL-13 --> Mast cell and Eosinophil degranulation via IgE --> Inflammatory mediators released --> Mucous production; Bronchial inflammation; Bronchoconstriction; Hypersensitivity of airways

Answer 37

``` Enzymes: Remodel CT (layer 4) • Tryptase • Chymase • Cathepsin G • Carboxypeptidase ``` Toxic mediator: Toxic to parasites; Increase vascular permeability; Anticoagulation; Smooth muscle contraction • Heparin • Histamine Cytokines: Inflammation; Cytokine production; Promote eosinophil and innate immune cell production • IL-4 • IL-5 • IL-13 Chemokines: Chemoattractant for monocyte, macrophages and neutrophils • CCL3 • CXCL9 ``` Lipid Mediator: SMC contraction; Increased vascular permeability; Stimulate mucous permeability; Bronchoconstriction ||| Attract leukocytes; amplify production of lipid mediators; activate platelets • PDG2 • PDGE2 • LTC4 • LTD4 • LTE4 • Platelet-activating factors (PAF) ```

Answer 38

* Inhaled allergens mediate specific IgE allergic reactions * Persistent allergens (PAMPs) activate epithelial TLRs * Epithelium secretes IL-25 and IL-33* * Activation of ILC Type 2 in submucosal tissue * ILC Type 2  IL-4, IL-5, IL-13 ≈ enhance Th2 and IgE response * Increased vascular permeability + chemoattraction: mast cell degranulation + chemokines  attract innate immune cells * Hyper-reactivity driving IgE and other mediators of inflammation * Resultant pathological changes: Irreversible airway damage and remodeling

Answer 39

* Dyspnea * Acute Chest Pain * Chronic cough (6 weeks

Answer 40

* Quick * Accessible * Identify range of pathologies

Answer 41

* Modest radiation dose | * Insensitive for causes of pathology

Answer 42

* Anteroposterior: XR from front to back | * Posteroanterior: XR from back to front

Answer 43

* Air * Fat * Water (soft tissues) * Bone * Metal

Answer 44

* Biologic density * Thickness of object * Density of material surrounding it

Answer 45

* Object in close contact with material of same density ≈ borders obliterated ≈ difficult to distinguish. * Usually material more radiopaque with object appearing radiolucent and outline accentuated

Answer 46

* Object of same radiographic density overlap but not in contact ≈ summation * Summation density

Answer 47

• Adjacent areas of differing contrast ≈ edge enhancement ≈ accentuation + artifactitious difference in radiographic density between two areas i) Positive (white) Mach Bands ii) Negative (black) Mach Bands

Answer 48

1) Silhouette Sign 2) Summation 3) Mach bands

Answer 49

``` 1) ID + Orientation • Who • What: Orientation • Where • Why • When ``` * Rotation: Sternal end of clavicle equidistant * Inspiration: Diaphragm at 10-11 posterior ribs on left * Penetration: IVD of mid-thoracic spine visible ``` 2) Summary • Cardiac monitor wires • Oxygen • Oxygen mask • NG tube • ETT • Venous lines - IJV: trace line from arm to axilla to SVC to heart and tip of line at cavoatrial junction - PICC: trace line from insertion (internal jugular or subclavian vein) towards heart ≈ cavoatrial junction • Cardiac devices • Intercostal catheters ``` ``` 3) Airways • Trachea position: Deviation? • Paratracheal masses • Carina: < 100º • Bronchi: Narrowed or Dilated ``` ``` 4) Breathing • Breathing: S approach in lung field • Lung volume: 10 ribs bilaterally • Zones: Symmetry, Density • Angles: Costophrenic recess (@ Costophrenic angle) and Costomediastinal recess • Cardiac borders: L + R ``` ``` 5) Circulation • Position • Size • Shape • Width • Hila: Position; shape; density ``` 6) Disability • Ribs • Clavicles + shoulders • Vertebral bodies: rectangular, space, x2 pedicles and disc space ``` 7) Everything Else • Gas under diaphragm (pneumoperitoneum) • Subcutaneous emphysema • Hiatus hernia • Absent breast shadow • Lung apexes clear • Lung pathology behind liver ```

Answer 50

Conduit for carrying deoxygenated blood from rest of body via IVC + SVC into RA and out of RV via pulmonary arteries to lung parenchyma to be oxygenated via diffusion then carry oxygenated blood from lung parenchyma (alveoli) to left atrium via pulmonary veins

Answer 51

* Blood transport * Protection from thrombi and emboli * Metabolism of vasoactive hormones: ACE; Inactivate BK, Serotonin, PGE1, PGE2, PGF2a; PGA1 and PGA2 pass through unaltered * Blood reservoir

Answer 52

``` 1) Pulmonary Circulation: • Low pressure ≈ 15mmHg • High flow • Low resistance • Mesh-like capillaries • Thin-walled, compliant arteries and veins ``` ``` 2) Systemic Circulation: • High pressure ≈ 120mmHg or MAP = 93mmHg • High flow • High resistance • Parallel capillaries ```

Answer 53

• Pulmonary vascular resistance falls with increased cardiac output thus inverse relationship 1) Capillary recruitment • Blood flow increasing ≈ pressure rises ≈ closed vessels open (e.g. apical lung region) ≈ resistance reduced ≈ increase GE + maintain gas exchange  2) Capillary distention • Blood flow increasing ≈ pressure rises ≈ thin and compliant pulmonary arterioles and capillaries ≈ capillary distention ≈ fall in pulmonary vascular resistance ≈ increase GE + maintain gas exchange 

Answer 54

* Maintains adequate gas exchange in times of increased demand: Opposed blood velocity tendency to speed up increased flow rate, maintaining time for pulmonary capillary blood to take up oxygen and dispose of carbon dioxide * Increase in capillary surface area: Increase capillary surface area ≈ increased gaseous exchange * Prevent pulmonary oedema: Reducing pulmonary vascular resistance ensures capillary pressure kept low ≈ prevent excess fluid leaking out from pulmonary capillaries

Answer 55

Fluid movement driven by hydrostatic forces which are normally weaker than colloid pressures allowing net movement of fluid into capillaries however surface tension works against this movement. Thus in diseases where deficient surfactant production occurs may result in pulmonary oedema

Answer 56

High lung volume during inspiration ≈ lowering of pleural pressure (more negative) ≈ ∆ transmural pressure ≈ extra-alveolar vessel dilates + alveolar vessels compressed ≈ increase pulmonary resistance    Benefits: GE increased: Decreased velocity of blood flow ≈ increased time for gas exchange to occur

Answer 57

• Low oxygen tension in alveoli (hypoxia) and/or pulmonary blood (hypoxemia) ≈ pulmonary vasoconstriction (hypoxia-induced pulmonary vasoconstriction) * Hypoxia-induced pulmonary vasoconstriction caused by hypoxia + hypoxemia * Hypoxia-induced pulmonary vasoconstriction augmented by hypercapnia and acidaemia/acidosis

Answer 58

Adenosine, Acetylcholine, Prostacyclin (PGI2) and isoproterenol

Answer 59

Serotonin, norepinephrine, histamine

Answer 60

Alveolar Hypoxia Types: 1) Regional Hypoxia • Hypoxia in one region of lung ≈ pulmonary vasoconstriction localised to specific region of lung ≈ diverted from poorly ventilated region ≈ minimises effect of gas exchange • Little effect on pulmonary arterial pressure • Alveolar hypoxia no longer exists ≈ vessels dilate and blood flow restored 2) Generalised Hypoxia • Hypoxia in large region of lung ≈ pulmonary vasoconstriction across lung ≈ pulmonary vascular resistance increases ≈ pulmonary hypertension • High pulmonary arterial pressure • Pathophysiological changes: Hypertrophy + Proliferation of smooth muscle cells, narrowing of arterial lumens and change in contractile function + right heart hypertrophy

Answer 61

Portion of vascular system comprising arterioles, capillaries and venules where nutrients, water, gases, hormones and waste products exchanged between blood and cells  

Answer 62

Regulates blood flow to individual organs, distribution of blood within organs and diffusion distances between organ blood supply and tissues and the exchange of fluid between intravascular and extravascular compartments  1) VSM: Partially constricted ≈ control blood flow  - All micro vessels   - Not capillaries 2) SNS: NE release by SNS ≈ myogenic mechanism intrinsic to smooth muscle   - Change diameter ≈ change vascular resistance  

Answer 63

1) Myogenic regulation: ∆ contraction or dilation based on microvascular pressure   • Fast • High pressure ≈ stretched VSM ≈ activate SAICs contract rapidly 2) Metabolic regulation: Driven by metabolic products • Increased BMR + low [O2] ≈ vasodilation of arterioles ≈ increased blood flow

Answer 64

* Low O2 * Low ATP * Increased adenosine * Increased CO2 * Increased H+ * Increased NO: NO Synthase metabolises L-arginine to NO ≈ activates GC ≈ cGMP * Lactic Acid

Answer 65

• Endothelin

Answer 66

Endothelin binds Type B endothelia receptors (GPCR) ≈ PLC ≈ PIP2 ≈ DAG + IP3 ≈ PKC activation + Bind channels ≈ constriction

Answer 67

* Alveolar surface tension: Pulls inwards ≈ draws fluid into interstitial space * Alveolar pressure: Compress interstitial space ≈ push fluid out of alveoli

Answer 68

• Myogenic arteriolar constriction in negative feedback ≈ lowers arterial pressure ≈ reduced elevation of hydrostatic capillary pressure ≈ reduced risk of oedema

Answer 69

High flow ≈ higher shear stress from blood against endothelial cells ≈ open potassium channels ≈ endothelial cell hyper polarisation ≈ increase calcium entry via electrical gradient ≈ elevated [Ca++] activates NO synthase ≈ increased NO ≈ blood vessels dilate

Answer 70

Blood flow stopped/reduced by vascular compression ≈ absence of blood ≈ hypoxia (low [O2]) ≈ vasodilatory chemicals accumulate + myogenic stimulation (low intravascular pressure driven) ≈ compression removed ≈ blood flow increased for a few minute as vasodilation following stoppage of flow

Answer 71

• Endothelial tube surrounded by basement membrane composed of dense connective tissue 1) Continuous • Basal membrane completely surrounds capillary   • Impermeable 2) Fenestrated • Windows • Bulk fluid exchange, permeable 3) Discontinuous • Absent regions of basement membrane • Exchange of large molecules

Answer 72

a) Diffusion-limited: Large molecules diffuse more slowly so rely on fenestrated or discontinuous capillaries   b) Flow-limited transport: Small molecules diffuse rapidly and therefore depend on rate of reaching exchange surface

Answer 73

Oedema (excessive fluid accumulation in interstitial spaces) ``` Causes of oedema: • Hypoalbuminemia (< 2.5g/100mL)   • Burns: destroy capillary integrity ≈ increased permeability and loss of albumin through damaged vessels   • Venous obstruction • Lymph channel obstruction ```

Answer 74

* Prevent fluid build-up: Mechanically collect fluid from tissue fluid (interstitial fluid) to prevent fluid accumulation and oedema * Collect proteins: Prevent exudate and water moving out of intravascular compartment to interstitium * Transport lymphatic fluid: Compression-relaxation cycle facilitating uptake and flow of fluid from interstitium into and down lymphatic channels

Answer 75

In heart failure, heart is failing as a pump ≈ CO reduced + arterial under-filling ≈ reduced renal perfusion ≈ reduced GFR ≈ sodium/electrolyte retention in interstitium ≈ water drawn out of intravascular volume into interstitium ≈ net driving force across the capillary ≈ fluid accumulation in the interstitium

Answer 76

Pulmonary Oedema Pulmonary oedema is caused by an abnormal increase in capillary pressure, capillary permeability or alveolar surface tension or a decrease in plasma colloidal osmotic pressure

Answer 77

Causes of Pulmonary Oedema: 1) Increased capillary hydrostatic pressure - E.g. High pulmonary venous pressure from mitral stenosis, left heart failure or heart attack 2) Increased capillary permeability - Pulmonary vascular injury from oxidant damage, inflammatory reaction or neurogenic shock  - Excess fluid and plasma proteins flooding interstitial paces and alveoli ≈ water drawn by osmosis into interstitial spaces 3) Increased alveolar surface tension - High surface tension lowering interstitial hydrostatic pressure ≈ increase in capillary fluid entering interstitial space

Answer 78

1) Cardiogenic | 2) Non-Cardiogenic

Answer 79

1) Zone 1: PA > Pa > Pv • Alveoli exceeds arterial pressure • Apex of lung • Occurs only in abnormal conditions whereby alveolar pressure increased (positive pressure ventilation), arterial pressure decreased (gravitational pull whilst standing or takeoff from spacecraft) 2) Zone 2: Pa > PA > Pv • Gravity causes lungs to be underperfused at apex and over perfused at base • Blood flow depends on difference between Pa • Blood flow greater at bottom cf top 3) Zone 3: Pa > Pv > Pa • Blood flow determined by arterial-venous pressure difference • Increase in blood flow primarily due to capillary distension

Answer 80

Exercise offsets gravitational effects in upright person: CO increases ≈ increased pulmonary arterial pressure ≈ capillary recruitment + distension in lung’s apex ≈ increased blood flow and minimising regional differences in blood flow in lungs

Answer 81

Gravity causes V:Q mismatching between ventilation and perfusion in the lungs

Answer 82

Air on side of alveolar-capillary membrane which does not partake in gaseous exchange ≈ wasted air ≈ physiological dead space

Answer 83

Blood on alveolar-capillary membrane which does not partake in gaseous exchange ≈ total amount of wasted blood (venous admixture) ≈ physiological shunt

Answer 84

• PEF: Absolute values - PEF Comparison  Standardisation for height, age, sex - PEF Diary: variability; Diurnal variations (Better at night) • Spirometry: Scalloping of expiratory flow volume loop; FEV1/FEVC < 0.7 - Airway inflammation --> obstruction --> lower FEV but FVC remains similar thus reduced ratio * Bronchodilator-response spirometry: Inhaled corticosteroid or ß2 agonist yields reversibility (12% improvement in FEV1 or FVC) * Bronchial provocation tests (BPT): Inhaled Mannitol (indirect) or Methacholine (PD20; Provocation Dose for 20% reduction) (direct) shows FEV1 decreased (15-20%) * Fractional Expired Nitric Oxide (FeNO) test: Elevated (> 50ppb; normal ≈ 25ppb) - Approximation of NO produced by eosinophils driven by Th2 response - FENO has a relatively decent sensitivity (88%) and specificity (79%) however peak flow and spirometry are both more specific (100%) specific but with lower sensitivity   * CXR: Normal; Hyperinflation; Rule out other pathologies * FBC: Possible eosinophilia, IgE * Blood culture: Aspergillus * Bronchoscopy: Normal; Look for structural abnormalities such as tracheomalacia or bronchomalacia

Answer 85

* Wheezing * Increased work of breathing * Features of atopy: dermatitis, allergic rhinitis * History of response to treatment within appropriate time frame * Dyspnea on exertion * Expiratory wheeze * Dry night-time cough

Answer 86

Peak expiratory flow rate ≈ PEF in one short, sharp breath    1) PEF Comparison  - Calibrated using diary  - Calibrated using peak flow standardisation for height, age and sex      2) PEF Diary   - Plot PEF changes - Change with treatments or activities etc   - PEF Diurnal Variation observed  

Answer 87

respiratory investigation assessing lung function measuring inhalation and exhalation, using FEV and FVC to diagnose asthma, COPD and other respiratory conditions 1) FEV = air exhaled in forced breath over 1 second   2) FVC = total amount of air exhaled during FEV test ≈ 6 seconds

Answer 88

 1) Normal: FEV / FVC = 0.7    2) Obstructive: FEV / FVC < 0.7  - More force required to get out full capacity of lungs in expiration ≈ lower FEV due to obstruction with FVC staying similar (but can change) ≈ lower ratio    3) Restrictive: FEV/FVC > 0.8   - Lung volumes limited overall ≈ FEV and FVC both decrease ≈ higher ratio

Answer 89

spirometry to assess baseline function then taking medication or performing exercise to measure lung function via spirometry which tests if airways are sensitive ≈ ∆ lung function Direct: Mannitol ≈ hypertonic stimulus = osmotic effect releasing inflammatory mediators from mast cells, basophils and eosinophils Indirect: Methacholine non-selective muscarinic receptor agonist in PSNS ≈ bronchoconstriction (PD20) Indirect: Exercise

Answer 90

PD20 ≈ Provocation Dose ≈ 20% decline in FEV

Answer 91

``` No vigorous exercise 30 mins before  - No tight clothing   - No smoking 1 hour before   - No heavy meal 2 hours before   - No alcohol 4 hours before  - Withhold medications as per instructed ```

Answer 92

Fractional Exhaled Nitric Oxide ≈ Quantitative, non-invasive investigation involving measurement of exhaled nitric oxide determining how much lung inflammation is present ≈ Th2 cells produce IL-4, IL-5 and IL-13 ≈ driver of inflammation (loosely related) ≈ activated eosinophils produce NO ≈ eosinophilic asthma indicator/ allergic asthma Normal: 25-50ppb (adults) cf 20-35ppb (children)    FENO has a relatively decent sensitivity (88%) and specificity (79%) however peak flow and spirometry are both more specific (100%) specific but with lower sensitivity

Answer 93

1) Control drivers of inflammation (U-GO-SEA) • Upper airway disease: sinus/polyps/rhinitis/sinusitis • GORD • Obesity • Smoking • Exposures: Cigarettes/dusts/occupational/infection • Allergies/Aero-allergens: Pets/pollen/Aspergillus/HDM ``` 2) Control inflammation • Steroids: Anti-inflammatory • Control upper airway disease • Antacids/anti-reflux • Infection avoidance, vaccination ```

Answer 94

* Recurrent Sx * Sx variability * Historical record of variable PEF or FEV1 * Recorded observation of wheeze * PMHx Atopy

Answer 95

1) High Asthma Risk • Treatment • Observe response 2) Intermediate Asthma Risk • Investigations to check variability (reversibility, PEF charting, BPT) + Eosinophilic inflammation or atopy (FeNO, Blood cultures, Skin-prick IgE) • Suspected asthma thus wait if asymptomatic or commence treatment if symptomatic 3) Low Asthma Risk • Other Ddx • Investigate differentials

Answer 96

* Low-dose inhaled corticosteroid (ICS): Budesonide (0.25-0.5mg/day nebulized); Fluticasone (100-200mcg/day) * Leukotriene Receptor Antagonist (LTRA): Monteleukast (4mg PO OD) * Long-Acting Beta Agonist: Salmeterol (50mcg BD) * Short-Acting Beta Agonist: Salbutamol (PRN) * Immunomodulator (Biologics): Omalizumab (Anti-IgE mAb)

Answer 97

``` Severities of Asthma: 1) Acute Severe Features • PEF: 33-50% predicted   • Cannot complete sentences in one breath   • RR > 25 breaths/min ≈ tachypnoea  • HR > 110 beats/min ≈ tachycardia ``` ``` 2) Life-threatening Features • PEF < 33% predicted or best • SpO2 <92% • Silent chest, cyanosis, feeble respiratory effort • Arrhythmia or hypotension • Exhaustion, altered consciousness ``` Management: 1) Patient Improving • Maintain treatment but change to 4-6 hourly for drugs 2) No Improvement in 15-30 minutes • Continue O2 and steroids • Use continuous nebulisation of salbutamol at 5-10mg/hour • Continue ipratropium 0.5mg 4-6 hourly until improvement   3) Still not improving • Discuss with ICU/HDU/ITU and Senior Clinician • Consider IV MgSO4 (bronchodilator) 1.2-2g over 20 minutes • Give nebulizer of salbutamol more frequently 15-30 minutes or 10mg per hour via continuous nebulizer

Answer 98

* Omalizumab: Anti-IgE mAb (Th2-hi asthma) * Dupilumab: Anti-IL-4 + IL-13 mAb (Th2-hi asthma) * Azithromycin: Reduces thymic stromal lymphopoeitin (TSLP) of Th2-hi asthma

Answer 99

Asthma Endotypes: 1) T2-lo asthma   • Th17 • Th1   Cytokines: IL-17, CXCL8, INFy, TNFa   2) Th2-hi asthma   • Th2 • ILC   Cytokines: IL-5, IL-4, IL-13

Answer 100

Interaction between upper and lower airway inflammation ≈ nasal stimulation ≈ afferent feedback to CNS ≈ efferent neurone stimulation via PSNS Vagal Nerve ≈ constriction oflower airways

Answer 101

50%-75% ≈ mild    33-50%: moderate    33% > ≈ severe

Answer 102

Discharge from hospital with consultant letter requires a 4 week review to review the peak flow (PEF) and compare to the normal and also what it was on discharge

Answer 103

Bronchial fremitus ≈ palpable vibration produced by breathing with partial airway obstruction

Answer 104

1) Rx working with bronchodilators   2) PEF and or FEV > 75% best or predicted   3) SpO2 > 94%  

Answer 105

1) Paraesthesia on medial aspect of upper arm due to brachial plexus impingement    2) Horner’s Syndrome (ptosis, miosis and anhidrosis) due to compression of sympathetic chain / sympathetic outflow to eye compromised

Answer 106

* Dilated blood vessels ≈ vasodilation   * Eosinophils   * Thickened BM * Mucus plug * Mast cells * Oedema * Hypertrophied smooth muscle   * Inflammatory infiltrate: mononuclear cells, eosinophils and mast cells)

Answer 107

1) Inhaled   - Site-specific   - Rapid response   - Smaller doses (as higher bioavailability)  - Reduced systemic/off-target side effects     Note: Efficacy of route dependent on type and severity of asthma, particle size of medicine and inhaler technique    2) Oral     3) IV

Answer 108

* MDI * BAI   * Accuhaler: dry powder which requires forceful inspiration to get dry powder to where required   * Spacer/aerochamber: large volume * Nebuliser: Use O2, compressed air or ultrasonic power to break drug solutions into fine mist delivered via respiratory tract through face-mask/mouthpiece  

Answer 109

1) Intermittent reliever   - SABA: 4mg with 8mg max day e.g. Salbutamol, Terbutaline 2) Regular preventer therapy   - ICS (low dose): 200-400mcg Beclomethasone or Fluticasone or Budesonide 3) Initial add-on therapy   - LABA: Salmeterol, Formoterol 4) Additional controller therapy  - LRTA: Monteleukast   5) Specialist therapies   - Specialist referral e.g. Omalizumab 

Answer 110

``` • Bind ß2r ≈ increase Gas ≈ cAMP ≈ PKA ≈ Increase contraction ≈ stimulate bronchial smooth muscle + inhibit mediator release from mast cells and infiltrating leukocytes ≈  - Bronchodilation  - Reduce breathlessness  - Increase air entry   - Reduce inflammatory process  ```

Answer 111

* Sympathomimetic effects * Muscle pain/cramps * Electrolyte disturbances (hypokalaemia) * Hyperglycaemia * Paradoxical bronchospasm (very rare) Reduce dose following side-effects; minimal bronchodilating dose 2mg-4mg

Answer 112

``` SABA: Salbutamol and Terbutaline • Fast acting • Short half life • Lasts < 5 hours • Reliever ``` ``` LABA: Salmeterol, Formoterol • Longer acting • Longer half life • Lasts ≈ 12 hours • Relieves bronchospasm at night or during exercise ```

Answer 113

* Sx using SABA 3 times per week < * Dyssomnia with wheeze or cough * Asthma attack in last 2 years

Answer 114

ICS binds GR (then chaperone protein transport) or diffuses across CSM ≈ ∆ transcription of genes in nucleus ≈ - Reduced cytokine production  - Reduced activation and recruitment to airways of inflammatory cells   - Inhibit generation of inflammatory prostaglandins and leukotrienes thus reducing mucosal oedema   - Decrease mucosal

Answer 115

* Oropharyngeal candidiasis (thrush) * Dysphonia (hoarseness of voice)  * OP (chronic high dose)  * Adrenal insufficiency * Growth retardation

Answer 116

* SAMA: Ipratropium | * LAMA: Umeclidinium

Answer 117

• SAMA or LAMA binds M3r antagonists ≈ competitive antagonist ≈   - Relaxation of bronchial smooth muscle  - Bronchodilation

Answer 118

* Dry Mouth * Difficult micturition * Increased intraocular pressure

Answer 119

• Monteleukast

Answer 120

* Asthma Sx when SABA and ICS used ± LABA * Exercise-induced asthma * Reduce early and late-phase bronchoconstriction responses to allergens

Answer 121

• LTRAs bind LTRA ≈ block LTRA ≈   - Block effect of cysteinyl leukotrienes in airways  - Reduced bronchoconstriction   - Reduce eosinophil recruitment to airways reducing inflammation, epithelial damage and airway hyperactivity

Answer 122

* Abdominal pain * GI symptoms: Diarrhea, Nausea, Vomiting * Increased URT infections * Hyperkinesia

Answer 123

* Theophylline | * Aminophylline

Answer 124

• Chronic, persistent asthma

Answer 125

• Methylxanthines ≈ PDE inhibitors + blocks adenosine receptors 1) PDE Inhibition  - PDE reduced inflammation  - Reduced inflammatory cells    2) Adenosine receptor blocker   - Bronchodilation   - Histone deacetylase ≈ immunomodulatory

Answer 126

* GI upset * Arrhythmia * CNS Stimulation E.g. Seizures * Hypotension

Answer 127

* ABX: Quinolones, Macrolides * Coffee * Chocolate

Answer 128

• Severe, persistent allergic asthma

Answer 129

• Omalizumab (Xolair) or Mepolizumab ≈ anti-IgE inhibiting mediator release from basophils and mast cells

Answer 130

* Anaphylaxis | * Increased risk of CVI/CHD/MI

Answer 131

Paradigm Shift in Treatment from one-size-fits-all to precision medicine model with multi-level patient stratification. Precision medicine allows delivery of right intervention to right patient at the right time

Answer 132

* Disease subtypes * Risk profiles * Demographics * Socioeconomic * Clinical features * Biomarker * Molecular sub-populations

Answer 133

* Genomics and Omics * Lifestyle * Preferences * Health history * Medical records * Compliance * Exogenous factors

Answer 134

* FHx of CF | * Caucasian (European ancestry)

Answer 135

• Autosomal recessive disease due to mutated CFTR causing reduced apical chloride secretion ≈ reduced osmotic gain and reduced mucous clearance ≈ accumulation of viscous mucous causing damage to respiratory and digestive systems

Answer 136

* Heel prick * IRT level --> non-specific, requires genome analysis * CFTR gene mutation

Answer 137

R117H is a mild mutation making which does not present in childhood in most heterozygotes with effect of R117H mutation varying according to intron 8 splice site efficiency ≈ lower thymine (Ts) in Intron 8 ≈ Exon9-CFTR mRNA ≈ dysfunctional CFTR protein

Answer 138

* Cascade testing * Prenatal Diagnosis (PND) * Pre-implantation Genetic Diagnosis (PGD)

Answer 139

Gene modifiers of Cystic Fibrosis --> Affect expression of other genes • CFM1: Meconium ileus: Bowel obstruction when meconium thickens • Pulmonary phenotype severity: TGFß1, TNF-a, HLA-II, MBL2 • Microbial infections: NOS1 • GI phenotype: Muc1

Answer 140

* R117H: reduced thymine (T) Intron 8 ≈ Exon9-CFTR mRNA ≈ dysfunctional protein * F508del: Deletion ≈ ∆CFTR ≈ reduced Cl- efflux ≈ viscous mucous accumulation * G551D: ∆CFTR ≈ reduced Cl- efflux ≈ viscous mucous accumulation

Answer 141

Ivacaftor Targets G551D

Answer 142

1) Small-Cell Lung Cancer • Cells near bronchi • Smoking • Aggressive thus poor prognosis 2) Large Cell Carcinoma • Any region of lung • Grows and spreads quickly ``` 3) Squamous cell carcinoma (30%) • Squamous cells of airways near bronchi • Smoking • Men > Women • Slow tumor growth ``` 4) Adenocarcinoma (40%) • Cells lining alveoli (connective tissue) • Common in non-smokers and smokers

Answer 143

Adenocarcinoma Cells lining alveoli Common in non-smokers and smokers

Answer 144

Small-Cell Lung Cancer Affects cells near bronchi

Answer 145

Large cell Carcinoma

Answer 146

Squamous cell carcinoma Affects squamous cells of airways near bronchi

Answer 147

1) Oncogenes • Dominant mutation • GOF • Excess cell survival and proliferation ``` 2) Tumour-suppresor genes • Recessive mutation • LOF • Multi-HIT hypothesis • Excess survival and proliferation ```

Answer 148

* Mutation in coding sequence: DNA/RNA/Protein activity * Gene amplification: DNA/RNA/Protein increased * Chromosome rearrangement * Change output: RNA/Protein * Change function (fusion): RNA (fusion)/Protein (fusion)

Answer 149

Epidermal Growth Factor Receptor (EGFR) ≈ ∆EGFR ≈ GOF ≈ Increased dimerisation ≈ increased AutoP + TransP ≈ triggers signal transduction cascade ≈ drives: MAPK; JAK-STAT; mTOR pathways ≈ cell proliferation, cell survival, migration, adhesion and differentiation

Answer 150

* Del747 | * T790M

Answer 151

• Epidermal Growth Factor Receptor (EGFR) ≈ ∆EGFR ≈ GOF ≈ Increased dimerisation ≈ increased AutoP + TransP ≈ triggers signal transduction cascade ≈ drives: MAPK; JAK-STAT; mTOR pathways ≈ cell proliferation, cell survival, migration, adhesion and differentiation

Answer 152

• Gefitinib: binds ATP binding pocket of tyrosine kinase ≈ prevent downstream signaling

Answer 153

Driver mutations: Drive tumour transformation/growth    Passenger mutations: Essential for tumour growth + survival Relevance: Find passenger mutations to target passenger mutations as secondary 

Answer 154

Clonality: Tumour cell with mutation replicates ≈ cell proliferation, survival and cell invasion ≈ identical tumour cells (with cancer stem cell characteristics) Resistance: Tumour cell has mutation ≈ ∆ action of EGFR ≈ Gefitinib no longer works ≈ cell survival, cell proliferation + cell invasion

Answer 155

- Host   - Pathogen  - Current techniques  - Imminent techniques  - Future strategies - Perspectives, public health, paradigm

Answer 156

1) Local defences failure • Barriers: skin, squamous, epithelium, uroepithelium • Clearance: tears, cilia, ducts, hollow organs • Physical conditions: acid, bile, lysozyme, orosomucoid (or alpha-1-acid glycoprotein a1AGP ≈ APP synthesised by hepatocytes) • Normal Flora 2) Innate immune response failure • Phagocytosis: Destruction + Oxidative burst  • Complement system: Phagocytic cell recruitment (C3a + C5a) + Phagocytosis (C3b) + MAC (C5b-C9) 3) Adaptive immune response failure • Immune activation: TNF, IL-1 and other cytokines ≈ CD4 Helper cells driven with IL-2 cytokines • B lymphocytes: Plasma cell and memory cell production • T lymphocytes: Cytotoxic cells, Killer cells, T8 suppressor cells

Answer 157

a) Primary Immunodeficiency: Genetic Defects 1) B cell immunodeficiencies: Reduced Ab ≈ severe recurret infections 2) T cell immunodeficiencies: Reduced B cell activation, microbe illing and signalling 3) Severe Combined Immune Deficiencies: T and B cell function decreased 4) Phagocyte disorders: Reduced phagocytosis, recurrent infections, Chronic Granulomatous Disease 5) Complement defects: Reduced complement proteins; may result in autoimmune condition development b) Second Immunodeficiency: Environmental factors 1) Malnutrition 2) Drug Regimens 3) Acute infection 4) Chronic infection

Answer 158

1) B cell immunodeficiencies: Reduced Ab ≈ severe recurret infections 2) T cell immunodeficiencies: Reduced B cell activation, microbe illing and signalling 3) Severe Combined Immune Deficiencies: T and B cell function decreased 4) Phagocyte disorders: Reduced phagocytosis, recurrent infections, Chronic Granulomatous Disease 5) Complement defects: Reduced complement proteins; may result in autoimmune condition development

Answer 159

1) Malnutrition 2) Drug Regimens 3) Acute infection 4) Chronic infection

Answer 160

Existence of microbial community in a dynamic state, vulnerable to stresses

Answer 161

A microorganism which can cause disease in the respiratory system   - Virus  - Bacteria   - Mycobacteria (Non-Tuberculous Mycobacteria)  - Fungi  - Other - Parasites

Answer 162

Pharyngitis Otitis media/Sinusitis Epiglottitis Croup

Answer 163

* S. pyogenes * Rhinovirus * N. gonorrhea * C. albicans * C. diptheriae * H. influenzae

Answer 164

* Local pain * Dysphagia * Odynophagia * Lymphadenopathy * Eustachian tube/sinuses occluded by inflammation

Answer 165

* Supportive treatment (if viral) | * ABX: Penicillin V or Macrolide (Erythromycin)

Answer 166

* S. pneumoniae * S. pyogenes * H. influenzae * M. catarrhalis * A. otitidis

Answer 167

* Pain * Fever * Pain worsens in evening and with head movement * Increased retrotympanic fluid levels with auroscope

Answer 168

* H. influenzae * S. pyogenes * Parainfluenza

Answer 169

* Dysphagia * High fever * Stridor * Drooling * Cherry red spot

Answer 170

* ABX: Cephalosporin * Intubation * Steroid * Emergency tracheostomy

Answer 171

CAP Pneumonia in Immunocompromised patients TB Bronchiectasis Bordatella pertussis Chronic Pulmonary Aspergillosis

Answer 172

* CXR * ABG * FBC: Leukocytosis * CRP * Sputum culture * NAAT * Ag detection (Immunofluorescence)

Answer 173

* Pneumocystis jirovecii * Aspergillus * M. tuberculosis * M. avian * Cytomegalovirus

Answer 174

* S. pneumoniae * Respiratory Syncitial Virus * Mycoplasma pneumoniae * Chlamydia trachomatis * Coronavirus (nCov-19)

Answer 175

* CXR * ABG * FBC: Leukocytosis * CRP * Sputum culture * Nasopharyngeal aspirate * Bronchoalveolar lavage * NAAT * Immunofluorescent Antibody Detection

Answer 176

Mycobacterium tuberculosis

Answer 177

* Genetic: Cystic fibrosis; Ciliary dyskinesia ± Kartagener’s Syndrome (ciliary dyskinesia, situs invertus and chronic sinusitis); alpha-1 antitrypsin deficiency; CT disorders; IBD; COPD and asthma; Focal bronchial obstruction * Immunodeficiency * Post-infectious: Measles/influenza/pertussis/Mycobacteria/Aspergillus

Answer 178

* CXR * CT-Chest * FBC * Sputum culture * Bronchial biopsy

Answer 179

Bordatella pertussis

Answer 180

* PCR of nasopharyngeal aspirate * Serology * FBC: WBC may be raised * Direct fluorescent antibody test

Answer 181

``` 1) Rapid diagnostics E.g. Molecular Bacterial Load Assay (MBLA) • Rapid diagnosis • Rapid treatment • ABX • Visualise viral load with MBLA ``` * Cost * Specificity and sensitivity may vary 2) Rapid Sequencing E.g. Whole Genome Sequencing * Cost * Speed * Logistics * Bioinformatics * Clinical utility * Cost * Accessibility 3) Breath analytics 4) Bacteriophages 5) Nanotechnology • Drugs delivered 6) Immunotherapy

Answer 182

- Cytokine secretion: IFN-a + IFN-ß ≈ protect cells + up-regulate MHC Class I for CD8 T(ctx) response  - Increase MHC class I expression + antigen presentation in all cells  - Activate DCs and macrophages  - Activate NK cells to kill virus-infected cells

Answer 183

* Respiratory epithelium * Goblet cells: Mucous production ≈ trap pathogen * Cilia: Beating cilia ≈ retrograde movement of pathogens to be swallowed and digested in GI or coughed out * Respiratory epithelium: Tight junctions ≈ impermeability and reduced diffusion rate * AMPs: ß-defensins ≈ kill pathogen * Cytokine secretion: Respiratory epithelium bind pathogen (PAMPs) via TLRs ≈ innate immune system activation

Answer 184

Route of Entry • Mouth and Respiratory Tract Mode of Transmission * Inhalation * Ingestion

Answer 185

Standard course of infection for a pathogen * Entry * Survival + transmission  * Attachment to surface of the host * Overcoming the body defences against infection e.g. capsule * Ability to damage the host e.g. toxin production or capsule ≈ virulence factors: Toxin secretion (toxigenesis)/ Pilus formation/ Capsule/ Adhesion/ Enzymes  

Answer 186

* Antigenic variation: Antigenic drift + Antigenic shift * Evasion of immune system: Virus encodes mutations which target APC, MHC processing and Humoral immunity * Immunoevasins * Dormancy

Answer 187

Nucleated cells up regulate cell surface proteins for acquired immune system to recognise foreign molecules ≈ upregulate MHC Class I ≈ antigen presentation to CD8 cytotoxic T cells * T cells * B cells * Macrophages * Dendritic cells * Neutrophils

Answer 188

Anucleated cells cannot upregulate MHC I class receptor e.g. RBC

Answer 189

1) Antigenic drift/shift (partial evasion/full evasion) • Change viral markers (haemaglutinin/cross-protective) ≈ reduce detection and presentation 2) Evade immune system • CMV: Encode chemokine receptor • HSV: Encode complement receptor/Encode Fc receptor • EBV: Encode homologue of IL-10 to inhibit Th1 lymphocytes 3) Immunoevasins: specialized viral proteins blocking viral peptide entry to ER for processing and placing into MHC class I to CD8+ cytotoxic T cells * HSV: ICP47/US6 * hCMV: US3 ``` 4) Dormancy: Latent viruses persist in the host by lying dormant, not replicating • HSV-1 • HSV-2 • HPV • HIV ```

Answer 190

- HSV-1 virus infects skin but cleared by immune system  - Residual infection persists in nuclei of sensory neurones serving infected tissue   - Virus transcribes part of genome ≈ LAT protein ≈ suppress lytic cycle + interferes with host cell apoptosis ≈ prolong life of cell  - Virus re-activated by environmental factors or other host conditions viral particles travel retrograde along neurones to tissue ≈ repeat infections e.g. cold sores on lips

Answer 191

Extracellular bacteria elicit Innate Lymphoid Cells (ILC) type 3 immune response involving TH17 and neutrophils  - Neutrophilic responses   - Drive opsonisation + complement fixing Abs - Production of AMPs   - MAMPs activating innate immunity  - Gram negative LPS activates TLR4  - Gram positive PDG activate TLR2, NOD1 and NOD2

Answer 192

Macrophages phagocytose bacteria breached barriers then phagosome fuses with lysosome and bacterium degraded ≈ APC to TH1 cells ≈ enhance macrophage activity + attract inflammatory infiltrate

Answer 193

Mycobacterium tuberculosis enters respiratory system via inhalation ≈ engulfed by alveolar macrophages ≈ Cord 1 prevents phagolysosome formation ≈ drives type 1 immune response ≈ chronic low level of infection ≈ TH1 CD4+ T cells + CD8+ T cells ≈ cytokines e.g. IFN-y ≈ drive granuloma formation ≈ central core of infected macrophages with MCG surrounded by large macrophages called epitheloid cells ≈ TNF-a ≈ core may become necrotic ≈ caseating  

Answer 194

Type 2 ILC-2 TH2 secretion of IL-4, IL-5, IL-13 ``` Cells: Granulocytes Mast cells Basophils Neutrophils ```

Answer 195

Type 1 ILC-1 Th1 (CD4+) and TctX (CD8+), IL-12; secreting IFN-y, IL-12 Cells: Macrophages Opsonising IgGs

Answer 196

* Nitrogen = 79% * Oxygen = 21% * Carbon Dioxide = 0.03% * Others = 1%

Answer 197

mmHg / 7.5 ≈ kPa

Answer 198

* Pressure of gas contributing to total pressure | * 21/100 x 760 = 160mmHg

Answer 199

* Inversely proportional * Altitude increases ≈ barometric pressure decreases ≈ pressure ∆ from 760mmHg ≈ Pressure < 760mmHg + oxygen concentration stays the same (21%) ≈ (21/100) x (Y < mmHg) ≈ reduced oxygen availability ≈ ∆ respiration gradients for gas exchange

Answer 200

* Pgas | * Solubility

Answer 201

* Alveolar gas saturated with water vapour so pH20 (≈ -47mmHg) reduces partial pressure of alveolar prior to multiplication against gas concentration * - 47mmHg PO2 Alveolar Gas Concentration • (760-47) x 21/100 = 150mmHg

Answer 202

1) Oxygen • Pulmonary circulation: Alveoli (100mmHg)  Blood (40mmHg) • Systemic circulation: Blood (100mmHg)  Tissues (< 40mmHg) 2) Carbon Dioxide • Pulmonary circulation: Blood (46mmHg)  Alveoli (40mmHg) • Systemic circulation: Tissues (> 46mmHg)  Blood (40mmHg)

Answer 203

* Stimuli * Sensors (Central + Peripheral Chemoreceptors) * Central Control (PONS, Medulla) * Effectors (Respiratory Muscles)

Answer 204

* Hypoxia: < 60mmHg --> peripheral chemoreceptors (Carotid + Aortic Bodies) --> Sinus Nerve of Hering to Glossopharyngeal Nerve (CN IX) and Aortic nerve to Vagus Nerve (CN X) --> inspiratory group (DRG) ± Pneumotaxic Centre (or Apneustic) * Hypercapnia: Increase PCO2  increase [H+] --> central chemoreceptors --> increase inspiratory center in medulla oblongata output * Acidosis: increase [H+] --> central chemoreceptors --> increase inspiratory center in medulla oblongata output

Answer 205

1) Voluntary Control: Cerebral cortex • Bypass respiratory control centres in brainstem via cerebral cortex, sending signals directly to motor neurons in spinal cord which innervate respiratory muscles 2) Reflex modification a) Pulmonary Stretch Receptors: Hering-Breuer reflex: Inspiration ≈ ∆ pulmonary stretch receptors ≈ afferent discharge inhibits inspiration b) Irritant receptors: Irritants (Smoke, dust, noxious gases…) ≈ detected by irritant receptors (free nerve endings between airway epithelial cells) ≈ initiate reflex bronchial + laryngeal constriction c) Juxta-Capillary Receptors: Change in interstitial fluid volume ≈ J-receptors detect ∆ in alveolar walls (close to capillaries) ≈ afferent impulses up Vagus never in slow conducting myelinated fibres ≈ rapid, shallow breathing d) Upper Airway Receptors: Mechanical + chemical stimuli ≈ upper airway receptors detect ∆ ≈ deep inspiration + closure of glottis ≈ pressure builds then expel via sneeze or cough

Answer 206

Hering-Breuer reflex: Inspiration ≈ ∆ pulmonary stretch receptors ≈ afferent discharge inhibits inspiration

Answer 207

J-receptors detect ∆ in alveolar walls (close to capillaries) ≈ afferent impulses up Vagus never in slow conducting myelinated fibres ≈ rapid, shallow breathing

Answer 208

* Joint and muscle receptors * Gamma System * Arterial baroceptors * Pain and temperature receptors

Answer 209

Involuntary response to mechanical or chemical stimuli detected by upper airway receptors or pulmonary irritant receptors in epithelium ≈ afferent impulses via Vagus Nerve to medulla oblongata ≈ efferent impulses via Phrenic or Intercostal nerves ≈ expel irritant via cough or sneeze

Answer 210

1) PONS (Modulate MO) | 2) Medulla Oblongata (Prime Driver of Ventilation)

Answer 211

a) Pneumotaxic Centre: DRG fire  Stimulation of Pneumotaxic Centre --> Terminates inspiration (tax) ≈ reduced inspiration depth but increased rate (as frequency is higher) b) Apneustic Area: Stimulation excites DRG --> prolong inspiration with long + deep breathes to control intensity of breathing --> increase tidal volume and reduce RR

Answer 212

a) Pneumotaxic Centre: DRG fire --> Stimulation of Pneumotaxic Centre --> Terminates inspiration (tax) ≈ reduced inspiration depth but increased rate (as frequency is higher)

Answer 213

b) Apneustic Area: Stimulation excites DRG --> prolong inspiration with long + deep breathes to control intensity of breathing --> increase tidal volume and reduce RR

Answer 214

Inspiratory Centre: Pre-Botzinger complex --> DRG --> contraction of diaphragm, external intercostal, SCM and anterior scalene --> inspiration --> firing ceases ≈ expiration

Answer 215

Expiratory Centre: DRG excites VRG --> VRG ≈ contraction: internal intercostals + abdominals ≈ forceful respiration Concept: VRG do not fire in normal, passive inspiration

Answer 216

1) Infectivity: Infectious vs Non-infectious 2) Location: URTI (Cough, Coryzal Sx) vs LRTI (Bronchitis, Pneumonia 3) Time: Acute (< 3 weeks), Subacute (3-8 weeks), Chronic (8 weeks)

Answer 217

Acute (< 3 weeks) | Subacute (3-8 weeks), Chronic (8 weeks)

Answer 218

* Hemoptysis * Smoker * Age: 55+ * Hoarseness * Fever * Weight loss * Dysphagia * Vomiting * Recurrent PNA

Answer 219

* Asthma * COPD * PNA * Post-infectious * Post-nasal drip * GORD * ACEi * Bronchitis * Whooping cough

Answer 220

* Tuberculosis * Bronchiectasis * Sarcoidosis * Interstitial Pulmonary Fibrosis * Methotrexate, Amiodarone, Rheumatoid lung

Answer 221

* Pneumonia: Sx = Fever, malaise, cough, pleuritic, chest pain, sputum (green/pink +/- haemoptysis); Signs = Pyrexia, tachycardia, confusion, hypotension, cyanosis, tachypnoea, rales, regional (lobar)/widespread * Lung Cancer: Sx = Chronic cough, haemoptysis, long term smoker, weight loss, malaise; Signs = cachexia, tachypnoea, supraclavicular nodes, low pitched wheeze * UACS/Post-nasal drip (Overlap with Rhinosinusitis): Sx = FOSIT, hoarseness/throat clearing/bad taste/blocked/runny nose; Signs = post-pharyngeal mucous, absence of chest signs * Post-infectious cough: Sx = FOSIT, hoarseness/throat clearing, halitosis; Signs: mucous may be purulent * GORD: Sx = cough, post-prandial exacerbation, associated with heartburn, reflux symptoms; Signs: Normal exam

Answer 222

* Cigarette smoking * Advanced age * Genetic factors: Anti-alpha trypsin * White ancestry

Answer 223

• Stimuli (smoking, reduced anti-alpha trypsin ≈ more trypsin) ≈ chronic inflammation ≈ narrowing + remodeling of airways, increased goblet cells, enlargement of mucous-secreting glands of central airways, vascular bed changes ≈ loss of elastin and alveolar integrity (emphysema)

Answer 224

* Cough (morning, productive) | * Dyspnea

Answer 225

* Sputum * Barrel chest (AP diameter increased) * Hyper-resonance on percussion * Distant breath sounds on auscultation * Poor air movement on auscultation (loss of lung elasticity and lung tissue breakdown) * Wheezing on auscultation * Coarse crackles (mucous and inflammation)

Answer 226

* Spirometry: FEV1/FEVC < 0.7 * SpO2: Low saturation * ABG: PaCO2 > 50mmHg; PaO2 < 60mmHg * CXR: Hyperinflation, increased AP ratio, flattened diaphragm, increased ICS, hyperlucent lungs * FBC: Raised Hct (polycythemia), possible raised WBC * ECG: Signs of RV hypertrophy, arrhythmia, ischemia * Alpha-1 antitrypsin level * Sputum culture

Answer 227

FEV1/FEVC < 0.7 Obstructive

Answer 228

* LAMA: Tiotropium (18mcg OD) * SABA: Salbutamol (100-200mcg 4-6 hours PRN) * ICS: Flutcasone (100/25 mcg OD) * Smoking cessation * Pulmonary rehabilitation * Long-term oxygen therapy

Answer 229

* LAMA: Tiotropium (18mcg OD) * SABA: Salbutamol (100-200mcg 4-6 hours PRN) * ICS: Flutcasone (100/25 mcg OD)

Answer 230

* Smoking cessation * Pulmonary rehabilitation * Long-term oxygen therapy

Answer 231

* Age > 65 years * Exposure to healthcare setting * COPD * Exposure to cigarette smoke * Poor oral hygiene * Use of acid-reducing drugs: PPIs * Alcohol abuse

Answer 232

``` S. pneumoniae Influenza virus S. aureus H. influenza M. pneumoniae L. pneumophila P. aeruginosa ```

Answer 233

• S. pneumoniae/Influenza virus/ S. aureus/H. influenza/M. pneumoniae/L. pneumophila/P. aeruginosa inhaled/aspiration/haematogenous spread from localized infection/direct extension from adjacent infected foci --> colonise respiratory epithelium --> Virulence factors + inoculum size > host factors --> consolidation, cough, pleuritic pain, cough and sputum

Answer 234

* Cough + sputum (mucopurulent = bacterial; scant/watery = atypical) * Dyspnea * Pleuritic chest pain * Fever * Confusion * Rigors/night sweats

Answer 235

* Abnormal auscultator findings: Crackles, decreased breath sounds, dullness to percussion * Bronchial breathing * Hyporesonance on percussion

Answer 236

* CXR: Consolidation shown by shadowing, cavitation, pleural effusion, multifocal consolidation * SpO2 < 94% * ABG: May show low PaO2 * U+E: Urea > 7mmol/L * FBC: Leukocytosis, WBC elevated * CRP: Elevated; > 100mg/L * LFTs: Normal or abnormal in Legionella pneumophilus infection * Blood culture * PCR * Urinary antigen testing for legionella and pneumococcus

Answer 237

Dependent on CRB65 score… Confusion + Respiratory Rate + Blood Pressure + Age (65) • CRB65 3 or 4: Urgent hospital admission

Answer 238

* Exposure to infection * Immunosuppression * Poverty * Malnutrition * Small community model (close contact) * Silicosis * Malignancy * Birth in an endemic country * HIV in appropriate areas

Answer 239

• M. tuberculosis (gram positive bacilli; non-motile; aerobic; Cord factor)

Answer 240

• Inhalation of M. tuberculosis ≈ exposure to respiratory epithelium --> alveolar macrophages (CD14+) phagocytose M. tuberculosis --> Cord factor (glycolipid in M. tuberculosis) ≠ autophagolysosome formation --> TB hides in macrophages --> IL-4, IL-13, TNF-a and TGFß-1 --> macrophage aggregation to form necrotic MGCs with cheese appearance (caseating) --> limit damage and bacterial dissemination (--> IFN-y deficiency ≈ impaired granuloma formation ≈ disseminated TB)

Answer 241

1) Primary TB i) Latent Tuberculosis: CXR; Serology ii) Active 1º TB: Sx, CXR and pathological findings 2) Secondary TB i) Reactivation TB: Endogenous reactivation or Exogenous reactivation 3) Drug-resistant TB: Multiple organs affected, inadequate combination therapy of drug concentration

Answer 242

* Cough: 2-3 weeks; dry  productive * Fever (low-grade) * Anorexia * Weight loss * Malaise * Night sweats

Answer 243

* Crackles * Bronchial breathing * Amphoric breath sounds (distant hollow breath sounds heard over cavities) * Clubbing * Erythema Nodosum

Answer 244

* CXR: Fibronodular opacities in upper lobes ± cavitation; atypical pattern if opacities in middle or lower lobes, hilar or paratracheal lymphadenopathy and/or pleural effusion * Sputum acid-fast bacilli (AFB) smear: 3 specimens, 8 hours apart  positive for AFB (M. avium and M. kansasii thus non-specific) * Sputum culture: Positive * FBC: Raised WBC; Low Hb; Elevated Eosinophils * NAAT: Positive for M. tuberculosis

Answer 245

Interpretation of TST  > 5mm positive: HIV positive; recent exposure; signs on CXR; > 10mm: high risk of reactivation (IV drug use, homelessness, endemic immigration, chronic illness, occupation); > 15mm: always positive, risk factors not needed

Answer 246

* Rifampin (antimycobacterial): 10mg/kg PO OD, maximum 600mg/dose * Isoniazid (antituberculosis): 5mg/kg PO OD, maximum 300mg/dose * Pyridoxine (vitamin B6): 25mg PO OD * Pyrazinamide: Calculated by lean body weight * Ethambutol (antituberculosis): Calculated by lean body weight * Isolation * Therapy monitoring

Answer 247

• Moxifloxacin + Kanamycin/Isoniazid/Pyrazinamide/Ethambutol

Answer 248

• Adrenal TB   - Clinical features: Adrenal insufficiency, Addison Disease Sx - DDx: CT/MRI ≈ bilateral adrenal cortex enlargement, medullary destruction with calcification, Abnormal labs (elevated ACTH) • Dermatological TB - Clinical features: Lupus vulgaris primarily on face; Painless reddish-brown nodules (apple jelly nodules) @ efflorescence • Urogenital TB - Clinical features: Dysuria, flank pain, haematuria, low-grade fever, prostatitis (males) or 2º amenorrhea and fallopian tube lesions - DDx: Sterile leukocytosis in 1st urine culture; Imaging: calcifications, strictures and cavities; Adnexal involvement: ID of M.tuberculosis in menstrual blood; Imaging: Pyosalpinx • Miliary TB = lymphohematogenous spread of M.tuberculosis from pulmonary and extra pulmonary focus with multiple organ involvement and small granola lesions   - Clinical features: CXR shows small, nodular densities of equal size throughout lung (millet seed appearance), CNS, choroid, skin, liver/spleen (HSM), kidneys, adrenal glands - Management: Normal TB Therapy + Surgical interventions

Answer 249

* 20-40 y/o * Scandinavian origin * FHx sarcoidosis * PMHx infection: M.tuberculosis, Mycoplasma, B. Burgdoferi, P. acnes)

Answer 250

• PMHx infection: M.tuberculosis, Mycoplasma, B. Burgdoferi, P. acnes)

Answer 251

Unknown • Genetic • Immunological • Infectious (Viruses; B. burgdoferi, P. acnes, M. tuberculosis, Mycoplasma)

Answer 252

• Alveolar macrophages secrete TNF-a, IL-2, IL-12, IL-4 and IL-13 and TGFß --> CD4 lymphocytes and CD8 lymphocytes attracted --> CD4 throughout granuloma and CD8 lymphocytes around periphery --> non-caseating due to minimal necrosis (MGCs); Fibrosis; Calcium dysregulation (macrophages produce 1-a hydroxylase)

Answer 253

* Systemic: Multisystem * Pulmonary: Lungs * Cutaneous: Plaques, lupus pernio * Ocular sarcoidosis: Anterior uveitis * Cardiac sarcoidosis: Heart block, CM * Neurosarcoidosis: Headaches, seizures

Answer 254

* Cough (non-productive) * Dyspnoea * Fatigue * Arthralgia * Photophobia (indicative of uveitis) * Red painful eye (indicative of uveitis) * Blurred vision (indicative of uveitis)

Answer 255

* Wheezing * Rhonchi (sonorous wheeze) * Lymphadenopathy * Photophobia (indicative of uveitis) * Red painful eye (indicative of uveitis) * Blurred vision (indicative of uveitis) * Erythema nodosum * Lupus pernio * Facial palsy (occurs with uveoparotid fever) * Heart block * Arrhythmias * Headache * Seizures * Hepatomegaly

Answer 256

* CXR: Hilar adenopathy, bilateral infiltrates, pleural effusions, egg shell calcifications, fibrosis * FBC: Anaemia, Leukopenia * U+E: Creatinine/Urea may be elevated if renal involvement * LFTs: Elevated AST and ALT (liver involvement) * Serum calcium: Hypercalcemia (granuloma produce 1a-hydroxylase and 1,25 hydroxyvitamin D3 * ECG: Conduction defects * Bronchoscopy: Non-caseating granulomas with MGCs * Bronchoalveolar lavage (BAL): Increased CD4+/CD8+ ratio * PFTs: Monitor disease ≈ Restrictive, obstructive or mixed pattern

Answer 257

* IV Corticosteroid: Methylprednisolone 40mg IV every 6 hours * Ventilatory support and oxygen

Answer 258

* Corticosteroid: Prednisolone 40mg PO OD | * Ventilatory support and oxygen

Answer 259

* Observation * Oral/Inhaled Corticosteroid: Prednisolone 20-40g PO OD for 1-3 months then reduce * (+ Adjunct) Methotrexate: 7.5mg PO OD increasing by 2.5mg per week to 15mg/week * (+ Adjunct) Oxygen: If SpO2 < 88%

Answer 260

* Topical corticosteroid: Triamcinolone topical 0.1% 2-4 times a day * Oral corticosteroid: Prednisolone 40mg PO OD * Hydroxychloroquine: 200-400mg PO OD

Answer 261

• Topical corticosteroid: Prednisolone ophthalmic (1%) 1 drop into affected eye QDS

Answer 262

* Oral corticosteroid: Prednisolone 40mg PO OD | * Cytotoxics: Methotrexate 7.5mg PO OD then 2.5mg per week until 15mg/kg

Answer 263

1) Lofgren Syndrome: acute presentation with fever + Bilateral hilar lymphadenopathy, Erythema nodosum, Migratory polyarthritis (BME) Sx triad 2) Heerfordt Syndrome: chronic clinical presentation with Parotitis, Uveitis, Facial palsy (PUF) triad

Answer 264

* Bilateral hilar lymphadenopathy * Migratory polyarthritis (symmetrical arthritis 1º affecting ankles) * Erythema nodosum (extensor surface of lower legs)

Answer 265

* Parotitis * Uveitis * Facial palsy

Answer 266

1) M3r Antagonists (LAMA + SAMA)    2) ICS    3) ß2 Agonists (SABA + LABA)

Answer 267

SAMA or LAMA binds M3r antagonists ≈ competitive antagonist ≈  - Relaxation of bronchial smooth muscle  - Bronchodilation  - Reduce mucous secretion  - Increase mucocilliary clearance  

Answer 268

- Dry mouth  - Difficult micturition ≈ urinary retention (in men)  - Constipation   - Nausea   - Headache   - Increase intraocular pressure ≈ worsen angle closure glaucoma

Answer 269

In allergen challenge

Answer 270

ICS - Inhaled Corticosteroids ≈ Regular preventer (anti-inflammatory and immunosuppressive) - Symptoms using SABA more than 3 times per week  - Dyssomnia with wheeze or cough  - Asthma attack in last 2 years  - Adherence  - Slower onset of action  - Longer term effects over months - reduction in airways responsiveness to allergens and irritants (including exercise)

Answer 271

1) Inhaled  - Beclomethasone  - Budesonide  - Fluticasone    2) Oral route (more severe asthma attack)  - Prednisolone   - Hydrocortisone (IV)

Answer 272

ICS binds GR (then chaperone protein transport) or diffuses across CSM ≈ ∆ transcription of genes in nucleus ≈  - Reduced cytokine production  - Reduced activation and recruitment to airways of inflammatory cells   - Inhibit generation of inflammatory prostaglandins and leukotrienes thus reducing mucosal oedema   - Decrease mucosal inflammation, widens airway and reduces mucous secretion

Answer 273

- Oropharyngeal candidiasis (thrush)   - Dysphonia (hoarseness of voice)  - OP (chronic high dose)  - Adrenal insufficiency  - Growth retardation

Answer 274

Oral: - Oropharyngeal candidiasis (thrush)   - Dysphonia (hoarseness of voice) Systemic:  - OP (chronic high dose)  - Growth retardation

Answer 275

 - Adrenal insufficiency

Answer 276

Steroid card if doses 800mcg ≤ of beclometasone (adults); 400mcg ≤ (children)  

Answer 277

- Methylxanthines - theophylline  - Mucolytics - carbocysteine ≈ reduce sputum viscosity  - PDE type 4 inhibitor ≈ Roflumilast - if severe COPD, repeated exacerbations  - Longterm ABX - Azithromycin  - Anti-IgE monoclonal antibody (Omalizumab)  - Long term Oxygen

Answer 278

``` - Sx  - ADL  - Exercise   - Symptomatic relief  - Spirometry: Changes in lung function  - Risk of exacerbations   ```

Answer 279

Collection of symptoms that bears symptoms of both asthma and COPD ≈ higher eosinophil, FEV1 swings, diurnal variation in PEFR, respond better to steroids (reducing exacerbation rate), more reversible to ß2 agonists

Answer 280

``` - Nebulise SABA or SAMA on air  - Oral ICS e.g. prednisolone  - ABX if infected   - Physio   - 24-28% oxygen  - Extreme: NIV or intubation ```

Answer 281

Asthma ``` Young age Exercise induced Nocturnal symptoms History of atopy (eczema) Obstructive picture Reversible on bronchodilators ```

Answer 282

COPD Heavy smoker Chronic sputum production Moderate COPD FEV1/FV1% - 52

Answer 283

Methotrexate lung (pneumonitis) Onset of symptoms after starting methotrexate Basal crepitaions suggest alveolar disease Restrictive pattern 71.6%

Answer 284

Alpa-1 antitrypsin deficiency Obstructive pattern Current non smoker Young age Family history

Answer 285

Restrictive Severe kyphosis would be an extra-pulmonary cause of a restrictive lung disease

Answer 286

FEV1 33% predicted FEV1/FVC = 87% This is a restrictive pattern

Answer 287

Pulmonary Tuberculosis

Answer 288

Bronchiectasis

Answer 289

PNA (Pneumonia)

Answer 290

ACE-i induced cough